Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract.
Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of beta-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance.
Cooper
Margaret A
MA
Department of Chemical Biology, Susan Lehman-Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Son
Alexander I
AI
Komlos
Daniel
D
Sun
Yuhai
Y
Kleiman
Norman J
NJ
Zhou
Renping
R
D022005:Adherens Junctions; D000818:Animals; D002386:Cataract / Q000209:etiology*; D002450:Cell Communication; D048430:Cell Shape; D036386:Ephrin-A5 / Q000172:deficiency / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D036104:Receptor, EphA2 / Q000502:physiology*; D036081:Receptors, Eph Family
D036386:Ephrin-A5; D036104:Receptor, EphA2; D036081:Receptors, Eph Family